Understanding the role of endogenous retroviruses (ERVs), which make up ~8% of the human genome, is essential for understanding genome biology and evolution. Despite their prevalence and considerable contribution to the human genome being known for quite some time, an exhaustive and critical analysis of the coding potential from genes encoded by ERVs has not been carried out. I predict that the envelope (Env) encoded by ERVs has evolved novel anti- retroviral properties in primates, as analogous host defense systems have been observed in rodents, sheep, and chicken. I propose to conduct a bioinformatics-based screen for coding potential encoded by Env genes, as this already shows a propensity towards co-option. Preliminary work has already identified 2 intriguing candidates. I will also functionally evaluate these and other Env with coding potential for anti-retroviral activity and elucidate the route of restriction. The work proposed here will uncover a novel host defense mechanism in humans and other non-human primates, and further elucidate the impact of ERVs on their host and their role in genome evolution.